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Dysregulation of inflammasomes serves a pathogenic role in autoinflammatory diseases (AIDs) and adult-onset Still's disease (AOSD) has been categorized as an AID. The present study investigated the expression of NLR family pyrin domain containing proteins (NLRPs) inflammasome in patients with AOSD, the effect of inflammasome inhibitors on NLRP3 signaling and whether human parvovirus B19-associated antigens can activate NLRP3 in patients with AOSD. mRNA expression levels of NLRPs in peripheral blood mononuclear cells (PBMCs) from 34 patients with AOSD and 14 healthy individuals were determined using reverse transcription-quantitative polymerase chain reaction. Protein expression of NLRP3 was evaluated by western blotting. Supernatant cytokine levels were measured by ELISA. Among the NLRPs investigated in the present study, NLRP3 transcripts were markedly elevated and expression of NLRP2, NLRP7 and NLRP12 was decreased in patients with AOSD compared with the controls. Treatment with NLRP3 inhibitors significantly reduced downstream NLRP3 signaling in PBMCs form patients with AOSD. B19-nonstructural protein (NS)1 stimulation of PBMCs from patients with AOSD induced significant upregulation of transcript levels of NLRP3, caspase-1 and interleukin (IL)-1ß compared with PBMCs from healthy controls. B19-NS1 stimulation of PBMCs from patients with AOSD induced significant increase in supernatant levels of IL-1ß and protein expression of NLRP3, caspase-1, IL-1ß, and IL-18 compared with healthy controls. Elevated expression of NLRP3 and its downstream inflammasome signaling components in patients with AOSD indicated a potential pathogenic role of B19-NS1. Thus, B19-NS1 may induce expression of IL-1ß and IL-18 through activation of caspase-1-associated NLRP3-inflammasome in AOSD. [ABSTRACT FROM AUTHOR]

Objective. To investigate the potential role of Th type 17 (Th17) cells and Th17-related cytokines in the pathogenesis of adult-onset Still’s disease (AOSD).Methods. The frequencies of circulating Th17 cells in 24 patients with active untreated AOSD, 16 patients with active SLE and 12 healthy volunteers were determined using intracellular cytokine staining and flow cytometry. Serum levels of Th17-related cytokines, including IL-1β, IL-6, IL-17, IL-18, IL-21 and IL-23 were measured by ELISA.Results. Significantly higher median frequencies of circulating Th17 cells were found in active untreated AOSD patients (1.01%) and active SLE patients (1.26%) than in healthy volunteers (0.12%, both P < 0.001). The frequencies of circulating Th17 cells were positively correlated with activity score (r = 0.527, P < 0.01) and serum ferritin levels (r = 0.724, P < 0.001) in AOSD patients, and correlated with SLEDAI (r = 0.663, P < 0.01) in SLE patients. Additionally, the frequencies of circulating Th17 cells were positively and significantly correlated with serum levels of IL-1β, IL-6, IL-17, IL-18, IL-21 and IL-23 in both AOSD and SLE patients. The frequencies of circulating Th17 cells and serum IL-17 levels significantly decreased after effective therapy in AOSD patients (both P < 0.001).Conclusion. Elevated frequencies of circulating Th17 cells and a positive correlation with disease activity in our AOSD patients suggest that Th17 cells contribute to the pathogenesis of this disease. Dysregulation of Th17 cells may be a common pathogenic mechanism that underlies the development of both AOSD and SLE. [ABSTRACT FROM PUBLISHER]

Objective. To determine circulating levels of CD4+CD25high regulatory T (Treg) cells and transforming growth factor-β (TGF-β) in patients with adult-onset Still's disease (AOSD) and to examine the associations with disease activity and clinical course of this disease. Methods. The frequencies of circulating CD4+CD25high Treg cells in 52 active AOSD patients, 42 active systemic lupus erythematosus (SLE) patients, and 22 healthy controls (HCs) were determined using flow cytometry analysis. Levels of serum TGF-β and soluble interleukin-2 receptor (sIL-2R) were measured by enzyme-linked immunosorbent assay. Results. Significantly lower levels of circulating CD4+CD25high Treg cells and serum TGF-β were found in AOSD patients and SLE patients than those found in HCs. Levels of circulating CD4+CD25high Treg cells and TGF-β were inversely correlated with disease activity scores for AOSD patients and SLE patients. Circulating CD4+CD25high Treg cell frequencies were positively correlated with serum TGF-β levels for patients with both diseases. Levels of circulating CD4+CD25high Treg cells and TGF-β significantly increased, paralleling clinical remission and the decrease in levels of C-reactive protein and soluble interleukin-2 receptor after effective therapy in AOSD patients. AOSD patients with monocyclic course had significantly higher levels of circulating CD4+CD25high Treg cells and TGF-β compared to those with polycyclic and chronic articular course. Conclusion. Diminished levels of circulating CD4+CD25high Treg cells and TGF-β, and inverse correlation with disease activity in patients with AOSD and SLE might be involved in the pathogenesis of both diseases. Increased levels of circulating CD4+CD25high Treg cells or TGF-β might be associated with a favorable clinical course in AOSD patients. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease, which has elevated autophagosome levels regulated by autophagy-related gene (ATG) expression. We investigated the associations of ATG polymorphisms with AOSD susceptibility, clinical manifestations, and disease course. The six-candidate single-nucleotide polymorphisms (SNPs) involved in autophagy were genotyped using direct sequencing on samples from 129 AOSD patients and 129 healthy participants. The differentially expressed gene products were quantified using PCR and ELISA. Significant linkage disequilibrium was noted in three SNPs of autophagy-related 16-like 1 (ATG16L1) gene (rs10210302, rs2241880, and rs1045100). Although the AA/CC/TT haplotype of ATG16L1 was not associated with the susceptibility of our AOSD patients compared with other haplotypes, those carrying this haplotype had lower mRNA expression levels of LC3-II, reflecting by autophagosome formation (p = 0.026). Patients carrying AA/CC/TT haplotype also have a significantly higher proportion of skin rash and a lower proportion of arthritis compared with other haplotypes. The AA/CC/TT haplotype was significantly associated with systemic pattern (odds ratio, 3.25; 95% confidence interval, 1.15–9.14; p = 0.026). In summary, the AA/CC/TT haplotype encoded lower levels of autophagosome formation and was associated with a higher proportion of skin rash and systemic pattern of AOSD compared with other haplotypes. [ABSTRACT FROM AUTHOR]